JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V20

 

Signalment (JPC #1850533): A lamb.

 

HISTORY: Fever (105^o F) and mild dyspnea.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Approximately 70% of the section is characterized by multifocal to coalescing areas where bronchial and bronchiolar epithelium exhibit one or more of the following changes: Marked epithelial hyperplasia with cells piling up to 10 layers thick with occasional mitoses; marked epithelial hypertrophy with cells enlarged 2-8 times normal with abundant eosinophilic granular cytoplasm and a large, up to 20 µm, vesiculate nucleus with a prominent nucleolus (karyomegaly); occasional intraepithelial, intranuclear, 10 µm, basophilic, smudgy viral inclusion bodies; epithelial single cell necrosis; and occasional neutrophil transmigration. Neutrophils occasionally expand the bronchial and bronchiolar submucosa, and bronchial and bronchiolar lumina contain variable amounts of an exudate composed of many viable and necrotic neutrophils, necrotic cellular debris, sloughed epithelial cells, fewer macrophages, and small amounts of fibrin. Multifocally adjacent alveoli are filled with an exudate composed of many viable and necrotic neutrophils, fewer macrophages, and small amounts of fibrin. Alveolar septa are mildly to moderately expanded by eosinophilic beaded to fibrillar material (fibrin), few neutrophils, and increased numbers of macrophages and lymphocytes, and are occasionally closely approximated (atelectasis). There is mild to moderate perivascular edema. 

 

MORPHOLOGIC DIAGNOSIS: Lung: Bronchitis and bronchiolitis, necrotizing and proliferative, subacute, multifocal, severe, with multifocal neutrophilic bronchopneumonia and epithelial basophilic intranuclear viral inclusion bodies, breed unspecified, ovine.

 

ETIOLOGY: Ovine Adenovirus

 

ETIOLOGIC DIAGNOSIS: Adenoviral pneumonia

 

GENERAL DISCUSSION:  

• Unencapsulated, icosahedral, double-stranded DNA virus; 70-90 nm diameter
• A generally host-specific subclinical infection that causes mild respiratory or enteric disease in a variety of species
• Associated with chronic enzootic pneumonia of sheep along with Mannheimia haemolytica, Pasteurella multocida, Parainfluenza Virus-3, reovirus, Respiratory Syncytial Virus, Chlamydia spp., and Mycoplasma ovipneumoniae
• Immunodeficiency is normally required in order to produce severe disease
• Seven different ovine viral species; sheep can be infected by bovine adenoviruses

 

PATHOGENESIS:  

• Virus is epitheliotropic and can be endotheliotropic, especially in ruminants
• Virus attaches to respiratory epithelium and enters cell > viral core migrates to the nucleus > virions produced in the nucleus > virions released by cell lysis
• Sloughed and hyperplastic bronchiolar epithelium may cause obstruction of airways leading to atelectasis
• Disruption of bronchiolar epithelium may lead to secondary bacterial infection

 

TYPICAL CLINICAL FINDINGS:  

• Non-specific respiratory signs: Fever, depression, nasal discharge, mild dyspnea
• Severity worsens with secondary bacterial infection, e.g. Mannheimia haemolytica

 

TYPICAL GROSS FINDINGS:  

• Cranioventral consolidation +/- atelectasis
• Typically complicated by secondary bacterial infection

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Virus isolation  
• Serology

 

ULTRASTRUCTURAL FINDINGS: 

 

DIFFERENTIAL DIAGNOSIS:  

• Parainfluenzavirus type 3 (Paramyxovirus) – Bronchointerstitial pneumonia that produces eosinophilic intracytoplasmic +/- intranuclear inclusion bodies and many multinucleated epithelial syncytial cells
• Should suspect adenovirus infection in sheep with bacterial pneumonia

• Parainfluenzavirus Type 3 – see above
• Maedi (small ruminant lentivirus/ovine progressive pneumonia, P-V17) – Severe interstitial pneumonia of older (>2 yrs) animals
• Jaagsiekte (ovine retrovirus, P-V16) – Well-differentiated pulmonary carcinoma with considerable nasal discharge

 

COMPARATIVE PATHOLOGY:  

Adenoviruses:

• Genus Mastadenovirus
  • Canine adenovirus type 1: Infectious canine hepatitis
  • Canine adenovirus type 2: Bronchointerstitial pneumonia with necrotizing bronchiolitis; clinical disease is usually a consequence of immunosuppression 
  • Bovine: Associated with respiratory and enteric disease in calves but not considered the primary pathogen in either syndrome (bovine adenovirus 1, 3, and 10)
  • Equine adenovirus types 1 and 2: Mild respiratory disease except in SCID Arabian foals where adenoviral infection leads to severe bronchiolitis and atelectasis
  • Porcine: Associated with encephalitis and diarrhea (porcine adenoviruses 1-5)
  • Mice: Host to 2 distinct adenoviruses both principally enterotropic – 

• Murine adenovirus-1 (MAdV-1) - Results in viremia and a fatal, multisystemic infection; infects cells of the monocyte–macrophage lineage, microvascular endothelial cells, respiratory epithelium, adrenal cortical cells, and renal distal tubular cells; BALB-scid and BALB-scid/beige mice develop fatal disseminated infection with focal hemorrhagic enteritis and microvesicular fatty change in the liver, consistent with Reye’s-like syndrome; B6-Rag1 mice develop disseminated disease with hemorrhagic encephalomyelitis; Athymic C3H/HeN-nude mice develop a progressive wasting disease with disseminated infection and duodenal hemorrhage
• Murine adenovirus-2 (MAdV-2) - Distinctly larger genome; athymic nude mice are clinically normal; gross lesions of MAdV-2 infection are not evident, except that juvenile mice may be bloated and runted; intranuclear inclusions in mucosal epithelial cells of the small intestine (distal segments, and the cecum; similar inclusions have been noted in adult nude mice without other detectable lesions
  • Rat: Incidental infection, no disease; lesions (intranuclear inclusions within small intestinal enterocytes) represent incidental findings
  • Hamster: Infection is subclinical; adenoviral intranuclear inclusion bodies have been observed in ileal enterocytes in tissues collected from hamsters during the first few weeks of life
  • Guinea pig: Adenoviral pneumonitis (Guinea pig adenovirus (GPAdV)) –Clinical disease primarily occur in the young, subclinical infections occur in adults; causes pulmonary disease and oval basophilic inclusion bodies (7–15 μm diameter) in respiratory epithelium; Histo: necrotizing bronchitis and bronchiolitis; Ddx: parainfluenza virus infections, cytomegalovirus infections, and bacterial infections of the lower respiratory tract (Bordetella bronchiseptica)  
  • Rabbit: Adenoviral enteritis documented in rabbits in Hungary; confirmed cases of adenoviral enteritis in rabbits appear to be confined to Europe, although naturally occurring seroconversion to bovine adenovirus (type 1) antigen has been detected in meat rabbits from multiple commercial colonies in Quebec, Canada
  • Non-human primates: Infection may be asymptomatic, or may exhibit a variety of clinical signs, depending on the tropism of the particular adenovirus.
    1. Respiratory: Cough, hyperpnea, dyspnea, and cyanosis, +/- keratoconjunctivitis. Most recover in 7-10 days. Histologic lesions similar to those in other species (bronchiolar and alveolar epithelial necrosis, enlarged nuclei with amphophilic to basophilic inclusion bodies, necrotic exudate).
    2. Pancreatitis: Adenoviral pancreatitis reported in rhesus monkey co-infected with SIV; necrosis of pancreatic acini, mononuclear infiltrates, interstitial fibrosis, and large, basophilic inclusions; INIBs seen in pancreatic ductal cells, duodenal glands, intestinal and gastric epithelium, and renal tubules, but necrosis and inflammation confined to the pancreas.
  • Pinnipeds: California sea lion adenovirus-1 (different from canine adenovirus-1) most commonly causes multifocal necrotizing hepatitis with hepatocellular intranuclear inclusions; Stellar sea lions have antibodies to CAV-1
  • Sheep: Ovine mastadenoviruses A and B (includes ovine adenoviruses 1-5, bovine adenovirus 2 and goat adenovirus 2)
    • Skunk adenovirus 1 (SkAdV-1) recent report that resulted in fatal bronchopneumonia in an African pygmy hedgehog (Needle, J Vet Diagn Invest. 2019)
    • Wildlife: Cervine adenovirus (Odocoileus hemionus deer adenovirus 1 (OdAdV-1) – proposed to be cervid atadenovirus A; cervid adenovirus 1) causes Adenovirus Hemorrhagic Disease of Deer in Oregon and California; produces pulmonary edema and erosions, ulcerations, hemorrhage or abscesses in the oral cavity (similar to Bluetongue virus and Epizootic Hemorrhagic Disease (orbiviruses)) with widespread vasculitis and endothelial intranuclear inclusions
    • Snakes and lizards: Subclinical or hepatitis, esophagitis, enteritis, splenitis, and encephalopathy (lizard atadenovirus A, snake atadenovirus A)
    • Chickens, ducks, geese: Egg drop syndrome (duck atadenovirus A; duck adenovirus 1)
    • Goats and sheep: Mild to no clinical disease (ovine atadenovirus D; goat adenovirus 1 and ovine adenovirus 7)
      • Helodermatid Adenovirus 2 – Recent report of pneumonia in a captive central bearded dragon with concurrent detection of Helodermatid Adenovirus 2 and a novel mycoplasma species (Crossland, Vet Pathol. 2018) 
      • Chickens: 
        • Inclusion body hepatitis (fowl adenovirus 2 (FAdV2), FAdV8, FAdV11))
        • Hepatitis-hydropericardium syndrome virus (FAdV4)
        • Gizzard erosion (FAdV1)
      • Quail bronchitis virus (fowl aviadenovirus A)
      • Turkey aviadenovirus B (turkey adenovirus 2 (TAdV2)
      • Ostrich: Fowl adenovirus serotype 8
      • Birds of prey: Falconid adenovirus-1
    • Frog siadenovirus A
    • Raptor siadenovirus A 
    • Turkey siadenovirus A (TAdV3)
      • Hemorrhagic enteritis (turkeys)
      • Marble spleen disease (pheasants)
      • Avian adenovirus splenomegaly (broilers) 
    • Psittacine adenovirus 2 – Encephalitis in cockatiels; no gross lesions, but histologic changes include degeneration of small blood vessels, endothelial necrosis, and INIBs in endothelial cells; usually minimal or absent inflammation; may also cause conjunctivitis, splenitis, hepatitis, nephritis, and pancreatitis as part of systemic disease.
    • Budgerigar adenovirus 1 – Hepatitis and encephalitis in budgerigars; histologic lesions in the CNS are as described for Psittacine adenovirus 2.
      • Gouldian finch adenovirus 1
      • Silawesi tortoise adenovirus 1
      • Includes adenoviruses of fish
    • Sixth proposed genus to include adenoviruses from turtles (Order Testudines)

                                                                                                                                                                                                                                                                                                                                                       

REFERENCES: 

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